iCVS-Inferring Cardio-Vascular hidden States from physiological signals available at the bedside.

Intensive care medicine is complex and resource-demanding. A critical and common challenge lies in inferring the underlying physiological state of a patient from partially observed data. Specifically for the cardiovascular system, clinicians use observables such as heart rate, arterial and venous blood pressures, as well as findings from the physical examination and ancillary tests to formulate a mental model and estimate hidden variables such as cardiac output, vascular resistance, filling pressures and volumes, and autonomic tone. Then, they use this mental model to derive the causes for instability and choose appropriate interventions. Not only this is a very hard problem due to the nature of the signals, but it also requires expertise and a clinician's ongoing presence at the bedside. Clinical decision support tools based on mechanistic dynamical models offer an appealing solution due to their inherent explainability, corollaries to the clinical mental process, and predictive power. With a translational motivation in mind, we developed iCVS: a simple, with high explanatory power, dynamical mechanistic model to infer hidden cardiovascular states. Full model estimation requires no prior assumptions on physiological parameters except age and weight, and the only inputs are arterial and venous pressure waveforms. iCVS also considers autonomic and non-autonomic modulations. To gain more information without increasing model complexity, both slow and fast timescales of the blood pressure traces are exploited, while the main inference and dynamic evolution are at the longer, clinically relevant, timescale of minutes. iCVS is designed to allow bedside deployment at pediatric and adult intensive care units and for retrospective investigation of cardiovascular mechanisms underlying instability. In this paper, we describe iCVS and inference system in detail, and using a dataset of critically-ill children, we provide initial indications to its ability to identify bleeding, distributive states, and cardiac dysfunction, in isolation and in combination.

Improving counterfactual reasoning with kernelised dynamic mixing models.

Simulation-based approaches to disease progression allow us to make counterfactual predictions about the effects of an untried series of treatment choices. However, building accurate simulators of disease progression is challenging, limiting the utility of these approaches for real world treatment planning. In this work, we present a novel simulation-based reinforcement learning approach that mixes between models and kernel-based approaches to make its forward predictions. On two real world tasks, managing sepsis and treating HIV, we demonstrate that our approach both learns state-of-the-art treatment policies and can make accurate forward predictions about the effects of treatments on unseen patients.

Improving Sepsis Treatment Strategies by Combining Deep and Kernel-Based Reinforcement Learning.

Sepsis is the leading cause of mortality in the ICU. It is challenging to manage because individual patients respond differently to treatment. Thus, tailoring treatment to the individual patient is essential for the best outcomes. In this paper, we take steps toward this goal by applying a mixture-of-experts framework to personalize sepsis treatment. The mixture model selectively alternates between neighbor-based (kernel) and deep reinforcement learning (DRL) experts depending on patient's current history. On a large retrospective cohort, this mixture-based approach outperforms physician, kernel only, and DRL-only experts.

Nonmonotonic Aging and Memory Retention in Disordered Mechanical Systems.

We observe nonmonotonic aging and memory effects, two hallmarks of glassy dynamics, in two disordered mechanical systems: crumpled thin sheets and elastic foams. Under fixed compression, both systems exhibit monotonic nonexponential relaxation. However, when after a certain waiting time the compression is partially reduced, both systems exhibit a nonmonotonic response: the normal force first increases over many minutes or even hours until reaching a peak value, and only then is relaxation resumed. The peak time scales linearly with the waiting time, indicating that these systems retain long-lasting memory of previous conditions. Our results and the measured scaling relations are in good agreement with a theoretical model recently used to describe observations of monotonic aging in several glassy systems, suggesting that the nonmonotonic behavior may be generic and that athermal systems can show genuine glassy behavior.

Furrows in the wake of propagating d-cones.

A crumpled sheet of paper displays an intricate pattern of creases and point-like singular structures, termed d-cones. It is typically assumed that elongated creases form when ridges connecting two d-cones fold beyond the material yielding threshold, and scarring is thus a by-product of the folding dynamics that seek to minimize elastic energy. Here we show that rather than merely being the consequence of folding, plasticity can act as its instigator. We introduce and characterize a different type of crease that is inherently plastic and is formed by the propagation of a single point defect. When a pre-existing d-cone is strained beyond a certain threshold, the singular structure at its apex sharpens abruptly. The resulting focusing of strains yields the material just ahead of the singularity, allowing it to propagate, leaving a furrow-like scar in its wake. We suggest an intuitive fracture analogue to explain the creation of furrows.

Multiple extinction routes in stochastic population models.

Isolated populations ultimately go extinct because of the intrinsic noise of elementary processes. In multipopulation systems extinction of a population may occur via more than one route. We investigate this generic situation in a simple predator-prey (or infected-susceptible) model. The predator and prey populations may coexist for a long time, but ultimately both go extinct. In the first extinction route the predators go extinct first, whereas the prey thrive for a long time and then also go extinct. In the second route the prey go extinct first, causing a rapid extinction of the predators. Assuming large subpopulation sizes in the coexistence state, we compare the probabilities of each of the two extinction routes and predict the most likely path of the subpopulations to extinction. We also suggest an effective three-state master equation for the probabilities to observe the coexistence state, the predator-free state, and the empty state.